All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Electrical stimulation of the stomach has been shown to modulate lower esophageal sphincter pressure. Electrical stimulation using neural gastrointestinal electrical stimulation (“NGES”) at high frequency can induce contractions of the smooth muscle of the gut.
The LES is a band of muscles at the junction of the stomach and the esophagus; when closed, the LES prevents the reflux of stomach contents into the esophagus. Gastroesophageal reflux disease (“GERD”) occurs when the LES does not close properly and stomach contents reflux into the esophagus. Increasing LES pressure may be useful in treating GERD.
Approximately 20% of the U.S. population experience weekly reflux symptoms. GERD is characterized by symptoms and/or tissue damage due to prolonged exposure of the esophagus to the acidic contents of the stomach. Two of the most common symptoms of GERD include chronic heartburn and regurgitation of acid. Chronic heartburn places a person at a greater risk for complications such as strictures, Barrett's esophagus (a pre-cancerous disease), and esophageal cancer. Approximately 10% of patients who have GERD develop Barrett's esophagus and of those patients, approximately 1% will develop esophageal cancer.
Treatment for GERD is maintained on a long-term basis, even after symptoms are brought under control. Current treatment methods include lifestyle changes, use of medications and surgical procedures. Lifestyle changes include avoiding factors that may aggravate the symptoms of GERD. Current medications available are promotility drugs to improve the movement of food from the stomach and increase LES pressure, H2 blockers to reduce acid production by the stomach and proton pump inhibitors to limit acid secretion in the stomach. H2 blockers and proton pump inhibitors allow resolution of symptoms and healing of the esophagus. Surgical treatment includes the Nissen's Fundoplication, which involves wrapping the stomach around the esophagus. Endoscopic treatments, when appropriate, are also available. In one endoscopic procedure, radiofrequency energy is delivered to the gastroesophageal junction to form scar tissue to strengthen the LES (i.e., the Stretta™ procedure). In another endoscopic procedure, sutures are use to alter the pathway between the stomach and esophagus (i.e., the EndoCinch™ procedure).
However, these treatment options carry disadvantages and shortcomings. Recently, two promotility agents, cisapride and tegaserod, were removed from the market due to potentially serious complications that had been reported. Nissen's Fundoplication is an invasive surgery and the new endoscopic treatments lack long-term data on their safety and success. Most drug therapies do not modulate LES pressure, which is an underlying cause of GERD. Thus, there exists a need for alternative treatment options for modulating LES pressure as well as for treatment of conditions caused by or related to abnormal LES pressure, including, for example, GERD.